Abstract
Study question
What’s the ploidy status of grade “C” blastocysts and what are their implantation potential and birthweight outcomes when tested euploid?
Summary answer
Grade “C” blastocysts were less likely to be euploid compared to grades “A/B”. Euploid “C”s led to reduced but reasonable implantation potential with similar birthweights.
What is known already
In contrast to grade “A” or “B”, grade “C” blastocysts are generally considered borderline quality in most in vitro fertilization programs, with inconsistent policies between clinics. Little evidence has been reported regarding their euploidy rate, implantation potential, and birthweight outcomes.
Study design, size, duration
This retrospective cohort study included 426 consecutive autologous-oocyte patients undergoing PGT-A (biopsy at day 5/6) at two associated private clinics between January 2013 and August 2020. A total of 1418 resulting blastocysts (tested either euploid or aneuploid) were analysed. Implantation outcomes were assessed in a subset of 520 singly transferred euploid blastocysts. Birthweight outcomes were evaluated in 209 singleton newborns using a gestation-adjusted Z score taking into account gestational age and baby gender.
Participants/materials, setting, methods
Blastocysts were graded “A/B/C” according to a combination of inner cell mass and trophectoderm morphology. Endpoints included ploidy, implantation and birthweight outcomes. Multiple regression (logistic or linear) was performed to investigate relative prognosis of grade “C” blastocysts using different endpoints in reference to grade “A/B” blastocysts, expressed as either adjusted odds ratio (aOR) or coefficients (β) with 95% confidence intervals (CI). Maternal age and biopsy day (5/6) were included as potential confounders at regression analysis.
Main results and the role of chance
Grade “C” blastocysts (n = 466) were associated with a lower euploidy rate in reference to either grade “A” (n = 179, aOR=0.412, 95% CI: 0.278–0.611, P = 0.000) or “B” blastocysts (n = 773, aOR=0.535, 95% CI: 0.418–0.685, P = 0.000). Euploid “C” grade blastocysts (n = 128) led to significantly reduced chance to implant when compared to either grade “A” (n = 90, aOR=0.387, 95% CI: 0.215–0.696, P = 0.002) or “B” blastocysts (n = 302, aOR=0.617, 95% CI: 0.404–0.944, P = 0.026); although implantation rate was still considered at a reasonable level (44.5%) as opposed to grades “A” (66.7%) or “B” (57.6%). However, no significant difference was observed in the birthweight (g, mean ± standard deviation) following the transfer of a single euploid grade “C” blastocyst (n = 42, 3310.8±704.1) in comparison to a single euploid grade “A” (n = 48, 3367.8±519.3, P > 0.05) or “B” blastocyst (n = 119, 3284.5±535.5, P > 0.05). Taking into account maternal age, biopsy day, gestational age and baby gender; further multiple linear regression analysis also showed similar results using either birthweight itself (C vs A, β=–52.395, 95% CI: –148.83–43.893, P = 0.282; C vs B, β=–104.338, 95% CI: –272.653–63.977, P = 0.223), or the gestation-adjusted Z score as an endpoint (C vs A, β = 0.101, 95% CI: –0.001–0.164, P = 0.052; C vs B, β = 0.084, 95% CI: -–0.073 – 0.241, P = 0.290).
Limitations, reasons for caution
The retrospective design of this study does not allow control for unknown confounders. Inner cell mass or trophectoderm was not graded separately making it difficult to further break down the “C” grade blastocysts. Only blastocysts suitable for biopsy were included for analysis, so results may not extrapolate to untested blastocysts.
Wider implications of the findings: Grade “C” blastocysts may still hold its clinical value despite reduced euploidy rate. PGT-A may be considered as a potential approach to utilize grade “C” blastocysts more effectively, without affecting birthweight outcomes. This is also potentially useful in patient counselling.
Trial registration number
Not applicable
Impact of maternal age on birthweight in frozen embryo transfer cycles: an analysis including 12565 singleton newborns
